In this application for a Mentored Clinical Scientist Development Award, Dr. Laurie M. McCormick will obtain expertise in the neuroimaging and neuropsychological assessment of patients with anorexia nervosa (AN) and how these measures relate to illness course and treatment response. AN is a severe psychiatric illness affecting a growing number of adolescent girls and young women, but its etiology is not well understood. Treatment of this illness is often prolonged and complicated by high relapse rates after hospitalization, emphasizing the need to identify features that predict treatment response. Previous research studies of patients with AN suggest that brain atrophy and neuropsychological deficits are present, but their relationship to each other and to clinical symptomatology is not well understood. It is also unclear whether these abnormalities resolve with adequate treatment or are stable vulnerability factors related to the development and maintenance of AN. Converging evidence suggests that the right dorsal anterior cingulate cortex (ACC) is involved with AN and our preliminary data have shown that this brain region is specifically reduced in patients hospitalized with AN, which correlates to neuropsychological dysfunction; and that normalization of gray matter volume in this brain region is related to outcome at 1- year post-hospitalization. Similarly, personality traits and features have also been linked to AN vulnerability, but the relationship of these traits to outcome and the neural underpinnings for these traits have not been fully elucidated. The University of Iowa Hospitals and Clinics has a well established eating disorders program for recruiting potential subjects as well as the neuroimaging resources and excellent mentors needed to complete the proposed study and contribute to the candidate's career development. Thus, her training will be integrated with a research project seeking to: (1) detect the presence of right dorsal ACC volume reduction as a neural correlate for specific neuropsychological deficits and abnormal personality factors in acutely ill patients with AN compared to age-matched normal controls; and (2) define the relationship between right dorsal ACC volume and neuropsychological normalization with treatment during hospitalization and outcome at 1-year post hospitalization. Neuroimaging will be completed with high resolution magnetic resonance imaging along with neuropsychological and personality/psychopathology assessments in young female adults with AN before and after treatment and at 1-year post-hospitalization compared to age and gender matched normal controls. Identifying the core neural underpinnings of AN to explain the pathophysiology of this disorder has clinical significance in its potential to improve the identification, prevention and treatment of AN. RELEVANCE (See instructions): In the United States, as many as 10 million females and 1 million males have an eating disorder such as anorexia nervosa, bulimia nervosa, or a combination of the two. Anorexia nervosa has one of the highest mortality and morbidity rates of any psychiatric illness, and the incidence of this disorder appears to be increasing. The clinical significance of this work is that it could bring to light the etiology of a very serious disease that has challenged medical professionals for over a century.